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Postnatal challenge dose of methamphetamine amplifies anticonvulsant effects of prenatal methamphetamine exposure on epileptiform activity induced by electrical stimulation in adult male rats.

Abstract
Administration of psychostimulants is often associated with increased seizure susceptibility. In our previous studies prenatal methamphetamine (MA) exposure increased seizure susceptibility of adult rats in models of primarily or secondarily generalized seizures induced by convulsant drugs. The effect of a single MA challenge dose in adulthood on chemically induced generalized seizures however, depends on the prenatal MA exposure history. Thus, the present study used a model of focal electrical stimulation to determine whether prenatal MA exposure with or without the adult challenge MA dose has the same outcome in a focal seizure model. Total of six groups of adult male rats were tested (prenatally MA-exposed, prenatally saline-exposed and rats without prenatal injections), each of these groups was either postnatally challenged with MA or with vehicle injection (MA-MA, MA-S; S-MA, S-S; C-MA, C-S). Seizures were induced by repetitive electrical stimulation (15 s/8 Hz) of sensorimotor cortex. Stimulation threshold, duration of afterdischarges (ADs), and presence and duration of spontaneous ADs (SAD) were evaluated. Additionally, behaviors associated with stimulation and ADs, and occurrence of wet-dog shakes (WDS) were analyzed. Our data demonstrate that daily injection of MA (5 mg/kg) within prenatal period decreased the occurrence of WDS and SADs, and shortened the duration of ADs and SADs suggesting anticonvulsant effects. Moreover, the challenge dose of MA (1 mg/kg) increased seizure threshold in all groups of rats, shortened duration of ADs in controls and prenatally saline-exposed animals, shortened duration of SADs in prenatally saline-exposed rats and totally eliminated WDS in all groups. Thus, the present study demonstrates that both chronic prenatal MA exposure and a single dose of MA in adulthood decrease focally induced epileptiform activity in adult male rats.
AuthorsKlára Bernášková, Iveta Matějovská, Romana Slamberová
JournalExperimental neurology (Exp Neurol) Vol. 229 Issue 2 Pg. 282-7 (Jun 2011) ISSN: 1090-2430 [Electronic] United States
PMID21349271 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2011 Elsevier Inc. All rights reserved.
Chemical References
  • Anticonvulsants
  • Central Nervous System Stimulants
  • Methamphetamine
Topics
  • Analysis of Variance
  • Animals
  • Anticonvulsants (pharmacology)
  • Behavior, Animal (drug effects, physiology)
  • Brain (drug effects, physiopathology)
  • Central Nervous System Stimulants (pharmacology)
  • Electric Stimulation
  • Electroencephalography
  • Female
  • Male
  • Methamphetamine (pharmacology)
  • Pregnancy
  • Prenatal Exposure Delayed Effects
  • Random Allocation
  • Rats
  • Rats, Wistar
  • Seizures (etiology, physiopathology)

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